We identified and structurally, biochemically and enzymologically characterized human immunodeficiency virus (HIV) protease, as well as its natural polyprotein substrates, in order to develop drugs that inhibit protease activity. It was known from our work on protease deficient MuLV mutants that when precursor polyproteins are not cleaved mature infectious virus can not be produced. Instead, noninfectious particles are made that, however, remain immunogenic because they carry complete envelopes. The idea underlying this research was to ultimately prepare chemical inhibitors that penetrate the infected cell, become incorporated into the budding virus, bind with high affinity to the viral protease or precursor polyproteins, prevent cleavage and lead to the production of non-infectious but still immunogenic viral progeny. The use of these chemical inhibitors would block the spread of HIV infection while allowing for antigenic stimulation of host immunity.